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Capsaicin, the pungent principal in red pepper, has been shown to damage small-diameter peptide-containing sensory neurons. Suppression of feeding by cholecystokinin octapeptide (CCK OP) was attenuated after systemic pretreatment with capsaicin. Capsaicin pretreatment did not attenuate suppression of food intake by intragastric preloads. Pretreatment of rats with microgram quantities of capsaicin injected into the fourth ventricle, near the sites of vagal afferent termination, also attenuated CCK OP-induced suppression of food intake. These results suggest that the satiety-inducing effects of CCK OP are mediated, at least in part, by capsaicin-sensitive afferent neurons.